tbuckley/cabot-search huggingface dataset:
Exosomes from young healthy human plasma promote functional recovery from intracerebral hemorrhage via counteracting ferroptotic injury
Authors: Wenqin Yang, Ning Ding, Ran Luo, Qian Zhang, Zhenhua Li, Fengchun Zhao, Shuixian Zhang, Xuyang Zhang, Tengyuan Zhou, Haomiao Wang, Long Wang, Shengli Hu, Guixue Wang, Hua Feng, Rong Hu
Journal: Bioactive Materials (2023)

Intracerebral hemorrhage (ICH), as a type of life-threatening and highly disabled disease, has limited therapeutic approaches. Here, we show that exosomes derived from young healthy human plasma exhibiting typical exosomes features could facilitate functional recovery of ICH mice. When these exosomes are intraventricularly delivered into the brain after ICH, they mainly distribute around the hematoma and could be internalized by neuronal cells. Strikingly, exosomes administration markedly enhanced the behavioral recovery of ICH mice through reducing brain injury and cell ferroptosis. MiRNA sequencing revealed that microRNA-25-3p (miR-25-3p) was differentially expressed miRNA in the exosomes from young healthy human plasma, compared with exosomes from the old control. Importantly, miR-25-3p mimicked the treatment effect of exosomes on behavioral improvement, and mediated the neuroprotective effect of exosomes against ferroptosis in ICH. Furthermore, luciferase assay and western blotting data illustrated that P53 as assumed the role of a downstream effector of miR-25-3p, thereby regulating SLC7A11/GPX4 pathway to counteract ferroptosis. Taken together, these findings firstly reveal that exosomes from young healthy human plasma improve functional recovery through counteracting ferroptotic injury by regulating P53/SLC7A11/GPX4 axis after ICH. Given the easy availability of plasma exosomes, our study provides a potent therapeutic strategy for ICH patients with quick clinical translation in the near future.
Complex modeling with detailed temporal predictors does not improve health records-based suicide risk prediction
Authors: Susan M. Shortreed, Rod L. Walker, Eric Johnson, Robert Wellman, Maricela Cruz, Rebecca Ziebell, R. Yates Coley, Zimri S. Yaseen, Sai Dharmarajan, Robert B. Penfold, Brian K. Ahmedani, Rebecca C. Rossom, Arne Beck, Jennifer M. Boggs, Greg E. Simon
Journal: npj Digital Medicine (2023)

Suicide risk prediction models can identify individuals for targeted intervention. Discussions of transparency, explainability, and transportability in machine learning presume complex prediction models with many variables outperform simpler models. We compared random forest, artificial neural network, and ensemble models with 1500 temporally defined predictors to logistic regression models. Data from 25,800,888 mental health visits made by 3,081,420 individuals in 7 health systems were used to train and evaluate suicidal behavior prediction models. Model performance was compared across several measures. All models performed well (area under the receiver operating curve [AUC]: 0.794-0.858). Ensemble models performed best, but improvements over a regression model with 100 predictors were minimal (AUC improvements: 0.006-0.020). Results are consistent across performance metrics and subgroups defined by race, ethnicity, and sex. Our results suggest simpler parametric models, which are easier to implement as part of routine clinical practice, perform comparably to more complex machine learning methods.
Prognostic value of extracellular matrix gene mutations and expression in multiple myeloma
Authors: Marietheres Evers, Martin Schreder, Thorsten Stühmer, Franziska Jundt, Regina Ebert, Tanja Nicole Hartmann, Michael Altenbuchinger, Martina Rudelius, Martin Kuric, Wyonna Darleen Rindt, Torsten Steinbrunn, Christian Langer, Sofia Catalina Heredia-Guerrero, Hermann Einsele, Ralf Christian Bargou, Andreas Rosenwald, Ellen Leich
Journal: Blood Cancer Journal (2023)
Weakly supervised deep learning to predict recurrence in low-grade endometrial cancer from multiplexed immunofluorescence images
Authors: Daniel Jiménez-Sánchez, Álvaro López-Janeiro, María Villalba-Esparza, Mikel Ariz, Ece Kadioglu, Ivan Masetto, Virginie Goubert, Maria D. Lozano, Ignacio Melero, David Hardisson, Carlos Ortiz-de-Solórzano, Carlos E. de Andrea
Journal: npj Digital Medicine (2023)

Abstract Predicting recurrence in low-grade, early-stage endometrial cancer (EC) is both challenging and clinically relevant. We present a weakly-supervised deep learning framework, NaroNet, that can learn, without manual expert annotation, the complex tumor-immune interrelations at three levels: local phenotypes, cellular neighborhoods, and tissue areas. It uses multiplexed immunofluorescence for the simultaneous visualization and quantification of CD68 + macrophages, CD8 + T cells, FOXP3 + regulatory T cells, PD-L1/PD-1 protein expression, and tumor cells. We used 489 tumor cores from 250 patients to train a multilevel deep-learning model to predict tumor recurrence. Using a tenfold cross-validation strategy, our model achieved an area under the curve of 0.90 with a 95% confidence interval of 0.83–0.95. Our model predictions resulted in concordance for 96,8% of cases (κ = 0.88). This method could accurately assess the risk of recurrence in EC, outperforming current prognostic factors, including molecular subtyping.
ABL1 kinase as a tumor suppressor in AML1-ETO and NUP98-PMX1 leukemias
Authors: Konstantin Golovine, Gleb Abalakov, Zhaorui Lian, Srinivas Chatla, Adam Karami, Kumaraswamy Naidu Chitrala, Jozef Madzo, Margaret Nieborowska-Skorska, Jian Huang, Tomasz Skorski
Journal: Blood Cancer Journal (2023)

Abstract Deletion of ABL1 was detected in a cohort of hematologic malignancies carrying AML1-ETO and NUP98 fusion proteins. Abl1−/− murine hematopoietic cells transduced with AML1-ETO and NUP98-PMX1 gained proliferation advantage when compared to Abl1 + /+ counterparts. Conversely, overexpression and pharmacological stimulation of ABL1 kinase resulted in reduced proliferation. To pinpoint mechanisms facilitating the transformation of ABL1-deficient cells, Abl1 was knocked down in 32Dcl3- Abl1ko cells by CRISPR/Cas9 followed by the challenge of growth factor withdrawal. 32Dcl3- Abl1ko cells but not 32Dcl3- Abl1wt cells generated growth factor-independent clones. RNA-seq implicated PI3K signaling as one of the dominant mechanisms contributing to growth factor independence in 32Dcl3- Abl1ko cells. PI3K inhibitor buparlisib exerted selective activity against Lin-cKit+ NUP98-PMX1; Abl1−/− cells when compared to the Abl1 + /+ counterparts. Since the role of ABL1 in DNA damage response (DDR) is well established, we also tested the inhibitors of ATM (ATMi), ATR (ATRi) and DNA-PKcs (DNA-PKi). AML1-ETO; Abl1−/− and NUP98-PMX1; Abl1−/− cells were hypersensitive to DNA-PKi and ATRi, respectively, when compared to Abl1 + /+ counterparts. Moreover, ABL1 kinase inhibitor enhanced the sensitivity to PI3K, DNA-PKcs and ATR inhibitors. In conclusion, we showed that ABL1 kinase plays a tumor suppressor role in hematological malignancies induced by AML1-ETO and NUP98-PMX1 and modulates the response to PI3K and/or DDR inhibitors.
Cystic fibrosis transmembrane conductance regulator modulators attenuate platelet activation and aggregation in blood of healthy donors and COVID-19 patients
Authors: Erik Asmus, Weronika Karle, Markus C. Brack, Corey Wittig, Felix Behrens, Leander Reinshagen, Moritz Pfeiffer, Sabrina Schulz, Bertina Mandzimba-Maloko, Lasti Erfinanda, Paul L. Perret, Laura Michalick, Patrick J. Smeele, Endry H.T. Lim, Charissa E. van den Brom, Alexander B.A. Vonk, Toralf Kaiser, Norbert Suttorp, Stefan Hippenstiel, Leif E. Sander, Florian Kurth, Ursula Rauch, Ulf Landmesser, Arash Haghikia, Robert Preissner, Harm J. Bogaard, Martin Witzenrath, Wolfgang M. Kuebler, Robert Szulcek, Szandor Simmons
Journal: European Respiratory Journal (2023)

<b>Cystic fibrosis transmembrane conductance regulator (CFTR) modulators reduce agonist-induced platelet activation and function. CFTR modulators, such as ivacaftor, present a promising therapeutic strategy in thrombocytopathies, including severe COVID-19.</b> https://bit.ly/3HJykdt
Inflammatory biomarkers in pulmonary arterial hypertension: ready for clinical implementation?
Authors: Thomas Koudstaal, Karin A. Boomars
Journal: European Respiratory Journal (2023)

<b>Boucly and colleagues provide further evidence for the involvement of the immune system in PAH and potential clinical applicability for three inflammatory biomarkers: β-NGF, CXCL9 and TRAIL</b>https://bit.ly/3CEgpDz
Statement on Tobacco 21 from the European Respiratory Society Tobacco Control Committee
Authors: Des W. Cox, Lauren Rodriguez, Jonathan Grigg
Journal: European Respiratory Journal (2023)

Tobacco consumption is the most significant cause of premature death across the European Union (EU) and is responsible for 700 000 deaths every year. Smokers are more likely than nonsmokers to develop lung cancer, COPD, coronary artery disease, stroke, diabetes, infertility and many other conditions 1]. According to Eurostat, 18.4% of people aged 15 years and over in the EU were daily smokers in 2019 [2]. Across Europe, the minimum age of sale of tobacco products is 18 years as per the obligations of the World Health Organization's Framework Convention on Tobacco Control (WHO FCTC). Data from the US Department of Health suggest that 90% of smokers begin smoking before the age of 18 years and we know that, overall, the average age to start smoking is 16 years of age. Furthermore, many young people in the upper age range of 18 to 21 years in some European countries, start smoking regularly after 18 years of age [3]. The ERS Tobacco Control Committee supports the Tobacco 21 initiative https://bit.ly/3YbqKP4
Effect of Nicotine Chewing Gum in Smoking Cessation
Authors: Agneta I. M. Hjalmarson
Journal: JAMA (1984)

The effect of 2-mg nicotine chewing gum as an adjunct to group therapy for smoking cessation was studied in a placebo-controlled, double-blind, randomized trial. After one year, 29% of the 106 subjects treated with nicotine chewing gum had remained abstinent throughout the year compared with 16% of the 99 subjects treated with placebo. The results were confirmed by measurement of levels of expired CO. More subjects in the nicotine group (70/94<i>v</i>45/93) reported that the gum reduced the craving for smoking. The adverse effects were few and not serious. In the nicotine group, 3% were still using the nicotine gum after two years. No subjects in the placebo group used the chewing gum beyond six months. Nicotine chewing gum is effective in improving the success rates in smoking cessation based on group therapy. (<i>JAMA</i>1984;252:2835-2838)
Coproexamination for Botulinal Toxin and Clostridium botulinum
Authors: Vulus R. Dowell
Journal: JAMA (1977)

Stool or serum specimens or both from 318 persons pertaining to 165 botulism investigations over a three-year period were examined. Botulinal toxin was detected in stools of 19 of 56 patients and in sera of 20 of 60 patients with clinical botulism; it was not detected in specimens from 246 persons with an illness other than botulism or well contacts of patients.<i>Clostridium botulinum</i>was identified in stools of 36 of 60 clinical botulism patients and in four of 27 asymptomatic contacts of patients with botulism victims, but not in stools of 65 persons not associated with confirmed botulism. When stool and serum samples were examined, confirmatory evidence was obtained for 72.9% of the botulism cases. Detection of botulinal toxin or<i>C botulinum</i>in the stool of a person should be considered evidence supporting the clinical diagnosis of botulism. (<i>JAMA</i>238:1829-1832, 1977)
Remarks of the President
Authors: Milford O. Rouse
Journal: JAMA (1968)

Each year at the opening session of the annual convention of the American Medical Association, it is the responsibility and privilege of the current President to offer a final report to the House of Delegates. Each man who stands in this honored place chooses the format for his own retiring address. The one I have chosen is a look at the year through which we have just come, then a short analysis of the present, followed by a brief examination of what we might expect in the years ahead. First, may I express our deep, heartfelt gratitude and appreciation for the many courtesies extended to Mrs. Rouse and me as we have had the privilege of visiting in practically every state of our great nation. The support of thousands of dedicated physicians and their wives has meant everything to us. Particularly would I also like to thank the members of
The Safety Effects of Child-Resistant Packaging for Oral Prescription Drugs
Authors: Gregory B. Rodgers
Journal: JAMA (1996)

<h3>Objective.</h3> —To evaluate the effectiveness of child-resistant packaging in reducing the mortality rate for children younger than 5 years from the unintentional ingestion of oral prescription drugs. <h3>Design.</h3> —Annual mortality rates for children younger than 5 years associated with the unintentional ingestion of oral prescription drugs are constructed for 1964 through 1992. The effect of child-resistant packaging on the child mortality rate during the postintervention period (1974 through 1992) is evaluated with a multivariate time series regression model. The analysis controls for changes in the consumption of oral prescription drugs over time and for long-term safety trends. <h3>Setting.</h3> —United States. <h3>Subjects.</h3> —Children younger than 5 years. <h3>Main Outcome Measure.</h3> —Estimated reductions in the child mortality rate associated with the use of child-resistant packaging. <h3>Results.</h3> —After controlling for covariates, the use of child-resistant packaging was associated with an annual reduction in the oral prescription drug—related mortality rate of 1.40 (95% confidence interval, 0.85-1.95) deaths per million children younger than 5 years. This suggests a reduction of about 460 child deaths from 1974, the year oral prescription drugs became subject to child-resistant packaging requirements, through 1992—a mortality rate reduction of about 45% from levels projected without the child-resistant requirements. <h3>Conclusion.</h3> —Child-resistant packaging reduces child mortality from the unintentional ingestion of oral prescription drugs. (<i>JAMA</i>. 1996;275:1661-1665)
A Multi-institutional Outbreak of Highly Drug-Resistant Tuberculosis
Authors: Thomas R. Frieden
Journal: JAMA (1996)

<h3>Objective.</h3> —To investigate a multi-institutional outbreak of highly resistant tuberculosis and evaluate patient outcome. <h3>Design.</h3> —Epidemiologic investigation of every tuberculosis case reported in New York City. <h3>Setting.</h3> —Patients cared for at all public and nonpublic institutions from January 1, 1990, to August 1, 1993 (43 months). <h3>Patients.</h3> —We reviewed medical and public health records and conducted clinical, epidemiologic, drug susceptibility, and restriction fragment length polymorphism (RFLP) analyses. A case was defined as tuberculosis in a patient with an isolate resistant to isoniazid, rifampin, ethambutol hydrochloride, and streptomycin (and rifabutin, if sensitivity testing included it), and, if RFLP testing was done, a pattern identical to or closely related to strain W. <h3>Main Outcome Measures.</h3> —Patient survival and the conversion of sputum cultures from positive to negative. <h3>Results.</h3> —Of the 357 patients who met the case definition, 267 had identical or nearly identical RFLP patterns; isolates from the other 90 patients were not available for RFLP testing. Among these 267 patients, 86% were human immunodeficiency virus (HIV)-infected, 7% were HIV-negative, and 7% had unknown HIV status. All-cause mortality was 83%. Epidemiologic linkages were identified for 70% of patients, of whom 96% likely had nosocomially acquired disease at 11 hospitals. Survival was prolonged among patients who recieved medications to which their isolate was susceptible, especially capreomycin sulfate, and among patients with a CD4<sup>+</sup>T-lymphocyte count greater than 0.200×10<sup>9</sup>/L (200/μL). Treatment with isoniazid and a fluoroquinolone antibiotic was also independently associated with longer survival. <h3>Conclusions.</h3> —This outbreak accounted for nearly one fourth of the cases of multidrug-resistant tuberculosis in the United States during a 43-month period. Most patients had nosocomially acquired disease, were infected with HIV, and unless promptly and appropriately treated, died rapidly. With appropriate directly observed treatment, especially combinations including an injectable medication, even severely immunocompromised patients had culture conversion and prolonged, tuberculosis-free survival.
Sequential or Alternating Doxorubicin and CMF Regimens in Breast Cancer With More Than Three Positive Nodes
Authors: Gianni Bonadonna
Journal: JAMA (1995)

<h3>Objective.</h3> —To improve current adjuvant results in patients with resectable mammary carcinoma and more than three positive axillary lymph nodes. <h3>Design.</h3> —A prospective randomized study was carried out to compare the effectiveness of four courses of doxorubicin hydrochloride followed by eight courses of cyclophosphamide, methotrexate, and fluorouracil (CMF) (sequential regimen) vs two courses of CMF alternated with one course of doxorubicin for a total of 12 courses (alternating regimen). All drug courses were recycled every 3 weeks. The median duration of follow-up at the time of current analysis was 9 years. <h3>Setting.</h3> —The study was conducted on patients operated on for primary unilateral breast cancer at the Istituto Nazionale Tumori of Milan, Italy. Adjuvant chemotherapy was delivered in the outpatient clinic of the Division of Medical Oncology. <h3>Patients.</h3> —A total of 405 women were entered into the study, 403 of whom met the protocol criteria. Patient characteristics were fairly well balanced between the two treatment groups, with the exception of extent of nodal involvement: 38% with more than 10 positive nodes were randomized to the alternating regimen compared with 29% in the sequential regimen (<i>P</i>=.08). <h3>Main Outcome Measure.</h3> —Relapse-free and total survival at 10 years after surgery estimated according to the Kaplan-Meier product limit method. <h3>Results.</h3> —Treatment outcome was significantly superior for patients who received the sequential regimen compared with those given the alternating chemotherapy. The relapse-free survival was 42% vs 28% (<i>P</i>=.002) and total survival was 58% vs 44% (<i>P</i>=.002), respectively. The benefit of the sequential regimen was evident in all patient subsets. Treatment was fairly well tolerated, but we documented four cases of congestive heart failure, which was fatal in two patients. <h3>Conclusions.</h3> —Current findings indicate that in women with extensive nodal involvement, sequential chemotherapy with doxorubicin followed by CMF yields superior results compared with the alternating administration of the same regimens or with classical CMF. (<i>JAMA</i>. 1995;273:542-547)
Antibiotics in Chronic Obstructive Pulmonary Disease Exacerbations
Authors: Sanjay Saint
Journal: JAMA (1995)

<h3>Objective.</h3> —A meta-analysis of randomized trials was performed to estimate the effectiveness of antibiotics in treating exacerbations of chronic obstructive pulmonary disease (COPD). <h3>Data Sources.</h3> —English-language studies published from 1955 through 1994 were retrieved using MEDLINE,<i>Index Medicus</i>, bibliographies, and consultation with experts. MEDLINE search terms included "COPD," "chronic bronchitis," and "antibiotic(s)." <h3>Study Selection.</h3> —Only randomized trials that enrolled patients having an exacerbation of COPD, used an antibiotic in the treatment group and placebo in the control group, and provided sufficient data to calculate an effect size were included in the meta-analysis. <h3>Data Extraction.</h3> —Descriptive and outcome data from each study were independently abstracted by two authors. <h3>Data Synthesis.</h3> —Overall summary effect size of the nine trials satisfying all inclusion criteria was 0.22 (95% confidence interval [CI], 0.10 to 0.34), indicating a small benefit in the antibiotic-treated group. Similar analysis of the six studies that provided data on peak expiratory flow rate changes revealed a summary effect size of 0.19 (95% CI, 0.03 to 0.35) and a summary change in peak expiratory flow rate of 10.75 L/min (95% CI, 4.96 to 16.54 L/min) in favor of the antibiotic-treated group. Sensitivity analyses did not significantly affect these results. <h3>Conclusions.</h3> —These analyses suggest a small but statistically significant improvement due to antibiotic therapy in patients with exacerbations of COPD. This antibiotic-associated improvement may be clinically significant, especially in patients with low baseline flow rates. (<i>JAMA</i>. 1995;273:957-960)
Effectiveness of a Violence Prevention Curriculum Among Children in Elementary School
Authors: David C. Grossman
Journal: JAMA (1997)

<h3>Objective.</h3> —To determine if a commonly used violence prevention curriculum, Second Step: A Violence Prevention Curriculum, leads to a reduction in aggressive behavior and an increase in prosocial behavior among elementary school students. <h3>Design.</h3> —Randomized controlled trial. <h3>Setting.</h3> —Urban and suburban elementary schools in the state of Washington. <h3>Participants.</h3> —Six matched pairs of schools with 790 second-grade and third-grade students. The students were 53% male and 79% white. <h3>Intervention.</h3> —The curriculum uses 30 specific lessons to teach social skills related to anger management, impulse control, and empathy. <h3>Main Outcome Measures.</h3> —Aggressive and prosocial behavior changes were measured 2 weeks and 6 months after participation in the curriculum by parent and teacher reports (Achenbach Child Behavior Checklist and Teacher Report Form, the School Social Behavior Scale, and the Parent-Child Rating Scale) and by observation of a random subsample of 588 students in the classroom and playground/ cafeteria settings. <h3>Results.</h3> —After adjusting for sex, age, socioeconomic status, race, academic performance, household size, and class size, change scores did not differ significantly between the intervention and control schools for any of the parent-reported or teacher-reported behavior scales. However, the behavior observations did reveal an overall decrease 2 weeks after the curriculum in physical aggression (<i>P</i>=.03) and an increase in neutral/prosocial behavior (<i>P</i>=.04) in the intervention group compared with the control group. Most effects persisted 6 months later. <h3>Conclusions.</h3> —The Second Step violence prevention curriculum appears to lead to a moderate observed decrease in physically aggressive behavior and an increase in neutral and prosocial behavior in school.
Nutritional Support of the Hospitalized Patient
Authors: Alexander E. Nehme
Journal: JAMA (1980)

Two groups of patients receiving total parenteral nutrition (TPN) were compared in a prospective study for a period of 24 months. The TPN in one group of 211 patients was exclusively managed by a nutrition support team. A variety of physicians managed the TPN of 164 patients in the other group. The complication rate of both groups was compared. The second group had a much higher incidence of all complications. The study concludes that a protocol strictly adhered to by knowledgeable persons is necessary for the proper administration of TPN in the hospitalized patient. (<i>JAMA</i>243:1906-1908, 1980)